Fig. 4
From: Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy
Hedgehog signaling pathway. a In the absence of Hh ligand, PTCH prevents activation of SMO. SMO cannot inhibit protein kinases including PKA, GSK-3β, and CK1. These protein kinases phosphorylate GLI protein in complex with SUFU resulting in cleavage of GLI into a repressed form. The repressed form will translocate to the nucleus inhibiting Hh target gene expression. b Hh ligand binds PTCH1 (transmembrane receptor). Smoothened (SMO) is relieved and inhibits proteolytic cleavage of GLI protein resulting in an active form. The active GLI protein translocates to nucleus and activates transcription factors. Cyclopamine binds to SMO preventing signal transduction to GLIS